miR-194-5p protects against myocardial ischemia/reperfusion injury via MAPK1/PTEN/AKT pathway

作者：Qiufeng Zhang, Xiaotian Wu, Jie Yang · 发表于：Annals of Translational Medicine · 年份：2021 · DOI：10.21037/atm-21-807 · 被引用次数：27 · 研究领域：Cardiac Ischemia and Reperfusion、Hydrogen's biological and therapeutic effects、MicroRNA in disease regulation

Background: MicroRNA (miRNA), which participates in various physiological and pathological processes, is a highly conserved small RNA sequence. This study aimed to investigate the role of miR-194-5p in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and myocardial ischemia/reperfusion (I/R) injury.Methods: We set up an H/R H9c2 cell model in vitro and an I/R mouse model in vivo. Then, cell vitality, apoptosis, and histopathological evaluation were conducted. Reactive oxygen species (ROS) generation and the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined by 2’,7’-Dichlorodihydrofluorescein diacetate (H2DCFDA), and enzyme-linked immunosorbent assay (ELISA), respectively. The level of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), myoglobin (Mb) is examined by ELISA. The expression of Caspase-3, cleaved-Caspase-3, Bax, Bcl-2, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and protein kinase B (AKT) was analyzed by western blot.Results: Data showed the expression of miR-194-5p was decreased in H/R-induced H9c2 cells and I/R-induced mouse. Conversely, overexpression of miR-194-5p could improve cardiomyocyte damage in ischemic models in vivo and in vitro. Furthermore, mitogen-activated protein kinase 1 (MAPK1) was found as a direct target of miR-194-5p, which negatively regulated the expression of MAPK1. The up-regulation of MAPK1 inhibited the myocardial protection previously observed by miR-194-5p.Conclus...